Dimethylformamide → Methyl 4-cyano-2-methylbenzoate

HRID 1970848Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][C:5]=1[CH3:11].[CH3:13][N:14](C)C=O>C1(C)C=CC=CC=1.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([C:13]#[N:14])=[CH:6][C:5]=1[CH3:11]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 4-bromo-2-methylbenzoic acid methyl ester (108 g, 471 mmol) in N,N-dimethylformamide (41) under a nitrogen atmosphere was added zinc (II) cyanide (88.5 g, 753.6 mmol) and tetrakis(triphenylphosphine)palladium(0) (65 g, 56.60 mmol). The reaction mixture was stirred at 100° C. for 16 hours. The reaction mixture was diluted with toluene and the phases were separated. The aqueous phase was extracted twice with toluene. The combined organic phases were washed with brine and saturated aqueous ammonium hydroxide, dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate/cyclohexane 1:5) to give 4-cyano-2-methylbenzoic acid methyl ester (73 g, 89% yield). 1H NMR (400 MHz, CDCl3): 7.78 (d, 1H), 7.52 (m, 2H), 3.92 (s, 3H), 2.62 (s, 3H).

Workup

customthe phases were separated
extractionThe aqueous phase was extracted twice with toluene
washThe combined organic phases were washed with brine and saturated aqueous ammonium hydroxide
dry with materialdried over sodium sulfate
concentrationconcentrated
customThe residue was purified by column chromatography on silica gel (eluent: ethyl acetate/cyclohexane 1:5)

Sources & evidence

ORD record: ord-67258e53816e4449bcdade2101385db0
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08431514B2

Reaction notes

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